title: Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes.
abstract: Helicobacter pylori infection is the major risk factor for gastric adenocarcinoma. The link with gastric adenocarcinoma is partly due to the H. pylori CagA oncoprotein. CagA is responsible for a particular cell phenotype in vitro, the 'hummingbird' phenotype, that corresponds to an elongation of the cells, mimicking an epithelial-mesenchymal transition (EMT). EMT participates in the carcinogenesis process, and is involved in the generation of cancer stem cells (CSCs). However, its involvement in gastric carcinogenesis has yet not been studied. Therefore, the aim of this study was to determine the role of H. pylori in EMT and in the emergence of gastric CSCs. For this purpose, gastric epithelial cells were cocultured with a cagA-positive H. pylori strain or its isogenic-deleted mutants or were transfected with CagA expression vectors. Study of the expression of epithelial and mesenchymal markers showed that H. pylori, via CagA, is responsible for an EMT phenotype associated with an increase in mesenchymal markers as well as CD44 expression, a known gastric CSC marker. Moreover, infection led to an increased ability to migrate, to invade and to form tumorspheres. Cell sorting experiments showed that only the CD44(high) cells induced by H. pylori infection displayed the mesenchymal phenotype and CSC properties in vitro, and had higher tumorigenic properties than CD44(low) cells in xenografted mice. Immunohistochemistry analyses on human and mouse gastric mucosa tissue samples confirmed a high expression of CD44 and mesenchymal markers in H. pylori-infected cases, and in gastric dysplasia and carcinoma. All of these data suggest that H. pylori, via CagA, unveils CSC-like properties by induction of EMT-like changes in gastric epithelial cells.
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: E
authors.initials: E
authors.lastname: Bessède
authors.affiliation: 1] 'RNA: Natural and Artificial Regulation' (ARNA) Laboratory, Université de Bordeaux, Bordeaux, France [2] INSERM, U869, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Staedel
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: L A
authors.initials: LA
authors.lastname: Acuña Amador
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: P H
authors.initials: PH
authors.lastname: Nguyen
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: L
authors.initials: L
authors.lastname: Chambonnier
authors.affiliation: Division of Microbiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hatakeyama
authors.affiliation: Pathology Department, Haut Leveque Hospital, University Hospital Center, Bordeaux, France.
authors.forename: G
authors.initials: G
authors.lastname: Belleannée
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Mégraud
authors.affiliation: 1] Université de Bordeaux, Laboratoire de Bactériologie, Bordeaux, France [2] INSERM, U853, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Varon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010641:Phenotype; D013270:Stomach; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000503:physiopathology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C080866:cagA protein, Helicobacter pylori